A large amount of genetic variation exists in the ovarian responsiveness to gonadotropins. We have found 5 to 7 fold differences in PMSG and hCG induced ovulation rate that are due to as few as 1 and 2 loci, respectively. A better understanding of the mechanisms which control genetic differences in ovarian function could result in the development of better controls of reproduction. We propose to determine the biochemical and physiological mechanisms which mediate major genetic differences in ovarian responsiveness to gonadotropins of five strains of mice. We plan to utilize a combination of in vivo and in vitro assays on these inbred strains as well as congenic, recombinant, inbred, F1, and F2 crosses of these strains. First, we will determine the genetic control of strain differences in gonadotropin induced ovulation rate. We will then determine whether these genetic differences are due to differences in 1) the number of follicles, 2) the rate of induction of follicle maturation, 3) the rate of induction of LH receptors and/or 4) the induction of ovulation. Finally, we shall examine the biochemical mechanisms which mediate the observed differences in the induction of follicle maturation, LH receptors or ovulation between 2 or 3 of these strains of mice. The proposed studies should: 1) reveal the nature of some of the normal genetic variation in ovarian function, 2) lead to a better understanding of the mechanisms of hormone action, and 3) expedite the development of improved methods for a more precise control of reproduction.